Lv Zhi-Dong, Yang Dong-Xia, Liu Xiang-Ping, Jin Li-Ying, Wang Xin-Gang, Yang Zhao-Chuan, Liu Dong, Zhao Jiao-Jiao, Kong Bin, Li Fu-Nian, Wang Hai-Bo
Center of Diagnosis and Treatment of Breast Disease, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, China.
Cell Physiol Biochem. 2017;44(5):1785-1795. doi: 10.1159/000485785. Epub 2017 Dec 6.
BACKGROUND/AIMS: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Our study investigated the functional role of miR-212-5p in TNBC.
Realtime PCR was used to quantify miR-212-5p expression levels in 30 paired TNBC samples and adjacent normal tissues. Wound healing and Transwell assays were used to evaluate the effects of miR-212-5p expression on the invasiveness of TNBC cells. Luciferase reporter and Western blot assays were used to verify whether the mRNA encoding Prrx2 is a major target of miR-212-5p.
MiR-212-5p was downregulated in TNBC, and its expression levels were related to tumor size, lymph node status and vascular invasion in breast cancer. We also observed that the miR-212-5p expression level was significantly correlated with a better prognosis in TNBC. Ectopic expression of miR-212-5p induced upregulation of E-cadherin expression and downregulation of vimentin expression. The expression of miR212-5p also suppressed the migration and invasion capacity of mesenchymal-like cancer cells accompanied by a morphological shift towards the epithelial phenotype. Moreover, our study observed that miR-212-5p overexpression significantly suppressed Prrx2 by targeting its 3'-untranslated region (3'-UTR) region, and Prrx2 overexpression partially abrogated miR-212-5p-mediated suppression.
Our study demonstrated that miR-212-5p inhibits TNBC from acquiring the EMT phenotype by downregulating Prrx2, thereby inhibiting cell migration and invasion during cancer progression.
背景/目的：三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型。我们的研究调查了miR-212-5p在TNBC中的功能作用。
采用实时定量PCR检测30对TNBC样本及其癌旁正常组织中miR-212-5p的表达水平。采用伤口愈合实验和Transwell实验评估miR-212-5p表达对TNBC细胞侵袭能力的影响。采用荧光素酶报告基因实验和蛋白质免疫印迹实验验证编码Prrx2的mRNA是否为miR-212-5p的主要靶标。
miR-212-5p在TNBC中表达下调，其表达水平与乳腺癌的肿瘤大小、淋巴结状态和血管浸润有关。我们还观察到，miR-212-5p表达水平与TNBC较好的预后显著相关。miR-212-5p的异位表达诱导E-钙黏蛋白表达上调，波形蛋白表达下调。miR-212-5p的表达还抑制了间充质样癌细胞的迁移和侵袭能力，同时伴随着向上皮表型的形态转变。此外，我们的研究观察到，miR-212-5p过表达通过靶向Prrx2的3'-非翻译区（3'-UTR）显著抑制Prrx2，而Prrx2过表达部分消除了miR-212-5p介导的抑制作用。
我们的研究表明，miR-212-5p通过下调Prrx2抑制TNBC获得EMT表型，从而在癌症进展过程中抑制细胞迁移和侵袭。
